Multinational phase 3 study of adding nivolumab to adjuvant chemoradiotherapy for high-risk LA-HNSCC

Postoperative cisplatin and radiotherapy is standard of care for high-risk resected locally advanced squamous cell carcinoma of the head and neck (LA-HNSCC). The phase 3 GORTEC 2018-01 NIVOPOST-OP trial, at 82 centers in six countries, evaluated adding nivolumab to adjuvant cisplatin and radiotherapy for LA-HNSCC with high risk of relapse. The trial included 680 patients (age 19-74 years, ECOG performance status 0 or 1) who were randomized 1:1 to three 3-week cycles of cisplatin and radiotherapy, or three 3-week cycles of nivolumab plus cisplatin and radiotherapy and six 4-week cycles of nivolumab. The primary endpoint was investigator-assessed disease-free survival. After median follow-up of 30.3 months, disease-free survival was significantly improved in the nivolumab group irrespective of PD-L1 expression (HR 0.76; p=0.034) with an increase in the rate of participants with treatment-related grade 4 adverse events (10% versus 5%). Treatment-related deaths occurred in two participants in each group. The authors conclude that nivolumab added to cisplatin and radiotherapy in high-risk resected LA-HNSCC improved disease-free survival with moderate toxic effect increase.